pralatrexate Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
folic acid analogues 4117 146464-95-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • 10-Propargyl-10-deazaaminopterin
  • pralatrexate
  • folotyn
Pralatrexate is a folate analog metabolic inhibitor that competitively inhibits dihydrofolate reductase. It is also a competitive inhibitor for polyglutamylation by the enzyme folylpolyglutamyl synthetase. This inhibition results in the depletion of thymidine and other biological molecules the synthesis of which depends on single carbon transfer.
  • Molecular weight: 477.48
  • Formula: C23H23N7O5
  • CLOGP: -0.11
  • LIPINSKI: 1
  • HAC: 12
  • HDO: 5
  • TPSA: 207.30
  • ALOGS: -4.43
  • ROTB: 10

  • Status: ONP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 0.53 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 2.70 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.33 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 15 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Sept. 24, 2009 FDA ALLOS
July 3, 2017 PMDA Mundipharma KK

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Malignant neoplasm progression 82.01 53.16 27 348 71514 53277177
Stomatitis 62.61 53.16 24 351 98134 53250557
Mucosal inflammation 56.38 53.16 18 357 42766 53305925

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Stomatitis 155.52 45.61 48 543 40181 32472754
Malignant neoplasm progression 96.05 45.61 40 551 78456 32434479
Mucosal inflammation 76.64 45.61 27 564 33407 32479528
Disease progression 54.69 45.61 28 563 86834 32426101
Platelet count decreased 50.08 45.61 29 562 114562 32398373

Pharmacologic Action:

SourceCodeDescription
ATC L01BA05 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ANTIMETABOLITES
Folic acid analogues
FDA EPC N0000175584 Folate Analog Metabolic Inhibitor
CHEBI has role CHEBI:35221 antimetabolite
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:50683 7,8-dihydrofolate reductase inhibitors

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Peripheral T-cell lymphoma indication 109977009
Stomatitis contraindication 61170000 DOID:9637
Liver function tests abnormal contraindication 166603001
Impaired renal function disorder contraindication 197663003
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Neutropenic disorder contraindication 303011007 DOID:1227
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.61 acidic
pKa2 5.29 acidic
pKa3 13.13 acidic
pKa4 4.6 Basic
pKa5 4.51 Basic
pKa6 1.39 Basic
pKa7 0.14 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
20MG/ML (20MG/ML) FOLOTYN ACROTECH N022468 Sept. 24, 2009 RX SOLUTION INTRAVENOUS 6028071 July 16, 2022 TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
40MG/2ML (20MG/ML) FOLOTYN ACROTECH N022468 Sept. 24, 2009 RX SOLUTION INTRAVENOUS 6028071 July 16, 2022 TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
20MG/ML (20MG/ML) FOLOTYN ACROTECH N022468 Sept. 24, 2009 RX SOLUTION INTRAVENOUS 7622470 May 31, 2025 TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
20MG/ML (20MG/ML) FOLOTYN ACROTECH N022468 Sept. 24, 2009 RX SOLUTION INTRAVENOUS 8299078 May 31, 2025 TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
40MG/2ML (20MG/ML) FOLOTYN ACROTECH N022468 Sept. 24, 2009 RX SOLUTION INTRAVENOUS 7622470 May 31, 2025 TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA
40MG/2ML (20MG/ML) FOLOTYN ACROTECH N022468 Sept. 24, 2009 RX SOLUTION INTRAVENOUS 8299078 May 31, 2025 TREATMENT OF PATIENTS WITH RELAPSED OR REFRACTORY PERIPHERAL T-CELL LYMPHOMA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Dihydrofolate reductase Enzyme INHIBITOR Ki 7.35 IUPHAR CHEMBL
Proton-coupled folate transporter Transporter IC50 7.24 CHEMBL
Folate transporter 1 Transporter IC50 9.16 CHEMBL
Folate receptor alpha Membrane receptor IC50 6.78 CHEMBL

External reference:

IDSource
4029347 VUID
N0000180303 NUI
D05589 KEGG_DRUG
4029347 VANDF
C1721300 UMLSCUI
CHEBI:71223 CHEBI
CHEMBL1201746 ChEMBL_ID
DB06813 DRUGBANK_ID
C418863 MESH_SUPPLEMENTAL_RECORD_UI
6840 IUPHAR_LIGAND_ID
8560 INN_ID
A8Q8I19Q20 UNII
148121 PUBCHEM_CID
662019 RXNORM
168008 MMSL
26748 MMSL
d07492 MMSL
013258 NDDF
428598004 SNOMEDCT_US
429320009 SNOMEDCT_US
895675003 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Folotyn Human Prescription Drug Label 1 48818-001 INJECTION 20 mg INTRAVENOUS NDA 27 sections
Folotyn Human Prescription Drug Label 1 72893-003 INJECTION 20 mg INTRAVENOUS NDA 29 sections
Folotyn Human Prescription Drug Label 1 72893-005 INJECTION 40 mg INTRAVENOUS NDA 29 sections